\ 


ARTIFICIAL  MUSKS: 

THE  STABILITY  OF  THE  ISOPROPYL 
GROUP  IN  CYMENEAND  ITS 
DERIVATIVES 

I1Y 


MORIS  HOWARD  JOFFE 


THESIS 

FOR  THE 


DEGREE  OF  BACHELOR  OF  SCIENCE 


CHEMICAL  ENGINEERING 


COLLEGE  OF  LIBERAL  ARTS  AND  SCIENCES 


UNIVERSITY  OF  ILLINOIS 


UNIVERSITY  OF  ILLINOIS 


Ua,j  c**x 


192 


THIS  IS  TO  CERTIFY  THAT  THE  THESIS  PREPARED  UNDER  MY  SUPERVISION  BY 


Yorie  Hcv.^rd  Jot:; 


2,  •,«+■  t 


J^TTj*jTJ  ,J  J . Jk.  - _ W ...  - » 


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IS  APPROVED  BY  ME  AS  FULFILLING  THIS  PART  OF  THE  REQUIREMENTS  FOR  THE 


DEGREE  OF 


Bachelor  of 


. Vy  *-  . U- 


Chemical  Engineering 

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C_c^^vJL_  JL  l 


Instructor  in  Charge 


Approv 


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CJL 


HEAD  OF  DEPARTMENT  OF 


Digitized  by  the  Internet  Archive 
in  2015 


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ACK1T  0 vVItSDGrBLIEIff  T 


In  writing  this  thesis  the  author  wishes  to 
acknowledge  his  indebtedness  to  Doctor  Carl  S.  Marvel, 
under  whose  supervision  this  work  was  done,  for  his 
numerous,  invaluable  suggestions,  for  his  interest  in  the 
work  and  for  his  ready  willingness  to  help. 


TABLE  OE  CONTENTS 


Page 


I.  Introduction  and  Historical  -- — ■ 1 

II*  Theoretical  — 3 

III.  Experimental 10 

IV.  Summary  17 


INTRODUCTION  AND  HISTORICAL 


Most  of  the  expensive  perfumes  are  unstable;  the  fragrance 
will  not  last,  ^uite  accidentlly  it  was  found  that  a small 
portion  of  ’mush'  will  prevent  decomposition  and  will  even  increase 
the  strength  of  the  fragrance.  LIusks,  then,  find  their  chief  use 
in  the  perfume  industries.  Natural  products  which  are  obtained 
with  difficulty  and  are  expensive  always  form  an  incentive  towards 
the  preparation  of  synthetic  or  artifical  products. 

When  one  speaks  of  a syntptie  or  artifical  product  one 
naturally  surmises  that  the  synthesized  compound  has  the  same 
composition  as  the  natural  product.  With  artifical  musks,  however, 
this  does  not  apply.  Natural  musks  have  been  studied,  yet 
little  is  known  as  to  their  structure.  It  has  been  determined 
that  the  active  principle  is  of  a ketonic  structure  and  that  it 
contains  no  nitrogen.  The  artifical  musk  is  a nitro-derivative 
of  the  benzene  series  and  resembles  the  natural  product  in  odor 
only. 

Among  the  foremost  of  investigators  in  synthesizing  artifical 
musks  was  Albert  Bauer.  Together  with  Thurgan  he  synthesized 

tri-ni tro-pseudo  butyl  toluene,  tri-nitro  pseudo  butyl  meta 

1 2 

xylene  , methyl  ether  of  tri-nitro  oxy  pseudo  butyl  methyl  benzene, 

dinitro  tertiary  butyl  xylyl  methyl  ketone,  methyl  ketone  of  tri- 


1.  B.  24,  2832-2843 

2.  B.  27,  1614-1619 


. 


-2- 


<7. 

nitro  pseudo  butyl  toluene  and  di-nitro  tertiary  bu.tyl  xylyl 
4 

aldehyde  . All  of  these  compound  smell  strongly  of  musk.  Kis 
work  was  followed  by  many  others  and  numerous  patents,  both  in 
Germany  and  France  were  issued  for  the  preparation  of  artifical 
musks . 

The  object  of  this  research  is  to  prepare  a product  having 
a strong  odor  of  musk,  using  cymene  as  the  base;  cymene  being 
chosen  because  of  its  comparative  cheapness. 

3.  B.  31,  1344-1349 

4.  B.  32,  3647-3648 


THEORETICAL  

Following  along  the  line  of  work  done  by  Baur  and  Thurgan, 

the  methyl  ketone  of  cymene  was  prepared"*-.  In  the  first  runs 

the  yield  was  very  poor  but  by  using  a mercury  seal  stirrer  and 

a three-necked  flask,  which  made  possible  the  introduction  of  the 

acetyl  chloride  slowly,  the  product  was  obtained  with  a yield 

of  62$.  In  large  runs  extreme  care  had  to  be  exercised  because 

of  the  large  amount  of  carbon  bisulphide  used  as  a solvent.  This 

ketone  was  then  nitrated.  For  nitration  purposes,  in  synthesizing 

ketone  musks,  Baur  used  100  $ nitric  acid.  Although  100  $ acid, 

as  a nitrating  agent  is  not  used  now.it  was  thought  advisable  to 

make  a run  using  Baur's  method.  Being  unable  to  obtain  the  acid 

its  preparation  was  tried,  but  the  attempt  proved  unsuccessful. 

The  problem  was  referred  to  the  research  department  of  the 

General  Chemical  Company,  but  was  reported  as  a failure.  This 

means  of  nitration  had  to  be  given  up  and  instead,  7 $ fuming 

sulphuric  acid  followed  by  fuming  nitric  acid  was  used. 

of 

The  results  obtained  by  nitration  'acetocymene  were  very 

A 

discouraging.  All  of  Baur's  compounds  possessed  a definite  cry- 
stalline form.  Acetocymene,  however,  on  nitration  came  down  as 
a gummy  mass,  which  could  not  be  crystallized  from  alcohol,  petrol- 

et/m 

ether,  benzene,  ethyl  acetate  or  a mixture  of  ethyl  acetate  and 
benzene.  The  mass  was  set  aside  for  six  weeks  and  then  a crystal- 
line compound  isolated  from  carbon  tetrachloride.  It  was  thought 
that  this  compound  was  a mono  or  dinitro  derivative  of  acetocymene, 


1.  Jour,  fxir  pr.  ch.  42,  508 


. 


, 


, 


— i3— 


but  tests  showed  that  the  compound  was  an  acid,  giving  a definite 
neutral  equivalent.  This  fact  seemed  so  out  of  the  ordinary  that 
the  preparation  of  further  artifical  musks  was  given  up  and  the 
determination  of  the  structure  of  this  compound  undertaken. 

The  nitration  of  acetocymene  was  repeated  to  obtain  the 
yield  of  crystalline  product.  Attempts  to  isolate  a solid  from 
carbon  tetrachloride  immediately  after  nitrstion  failed.  It  seemed 
that  some  "aging"  is  required  before  a separation  can  be  made. 

In  1920  A If than ^ , a German  chemist*  studied  the  nitration 
products  of  cymene  and  toluene.  He  found  that  cymene  on  nitration 
gave  2,6  din itro cymene  and  also  2,4  dinitro  toluene.  In  the 
latter  case  the  iso-propyl  group  is  first  oxidized  to  the  acid 
and  then  the  carboxyl  group  is  replaced  by  a nitro  group.  He 
also  found  that  p-acetfi) toluene  upon  nitration  gave  2,6  dinitro- 
p toluic  acid. 

The  product  which  was  obtained  by  nitrating  acetocymene 
dissolves  in  sodium  hydroxide  and  gives  a neutral  equivalent. 

From  previous  work  on  cymene  the  following  possibilities  for  its 
structure  suggest  themself. 


I 


C-OH  QN 


hC^ch3 
J Z68 


B.  53B,  178 


, ' « * Jig  i 


, 


-4- 


All  three  possibilities  contain  two  nitro  groups.  The  analysis 
for  nitrogen  clearly  verifies  this  assumption.  The  neutral 
equivalent  of  263,  that  was  obtained  eliminates  formula  I.  The 
analysis  for  C eliminates  formula  II;  formula  III  then  remains. 
The  nitrated  product  was  oxidized  using  potassium  permanganate  in 
alkaline  solution  as  the  oxidizing  agent.  A white  ciystalline 
product  melting  sharply  was  obtained.  A neutral  equivalent  was 
taken  which  showed  the  presence  of  two  carboxyl  groups.  If 
formula  III  were  correct  the  oxidation  product  should  be 


From  previous  work  it  has  been  shown  that  the  isopropyl  group  is 
unstable  and  will  be  oxidized  first.  An  analysis  of  the  oxidation 
product  showed  the  presence  of  only  one  nitro  group  and  the 
neutral  equivalent  and  the  analysis  for  carbon  did  not  check 
with  the  above  formula.  The  only  other  possibility  is  that  one 
nitro  group  has  entered  the  isopropyl  group,  which  on  oxidation 
was  removed. 

The  following  structure  was  assigned  to  the  crystalline  product 
isolated  from  the  nitration  of  acetocymene.  All  analysis  verify 


CHj 


NOH 


Hf^CHd 


- 


— 5— 

this  assumption. 

The  stability  of  the  isopropyl  group  in  all  of  the  previous 
work  was  not  of  the  same  degree.  The  author  set  out,  therefore, 
to  determine  what  properties  or  conditions  were  necessary  to 
make  the  isopropyl  group  in  cymene  or  its  derivatives  stable 
towards  the  action  of  the  nitrating  agent,  sulphuric  acid-nitric 
acid. 

1 

P- cymene  treated  with  chlorine  forms  monochloro- cymene. 

This  on  nitration  gives  2- chloro-dinitro cymene.  The  yield  was 

high,  although  a small  amount  of  oxidation  product  was  obtained, 
b 2 

Again,  when  tymol  was  nitrated  , trinitro- thymol  was  not  obtained. 
Instead,  the  isopropyl  group  was  removed  forming  trinitro-m- 
cresol.  Mr-  Zellhoefer,  of  our  laboratories,  nitrated  the 
methyl  ether  of  "thymol  and  obtained  the  methyl  ether  of  tri-nitro- 
a-cresol . 

These  works  as  well  as  the  work  on  cymene  led  to  the  belief 
that  the  group  meta  to  the  isopropyl  group  had  some  definite 
relation  to  the  stability  of  that  group.  So  many  ideas  have 
been  set  forth  that  nothing  definite  has  as  yet  been  determined 
along  this  line.  With  these  points  in  view  the  second*  step  in 

V 

this  research  was  begun. 

Since  the  -COOH^  group  in  acetocymene  on  nitration  was 
oxidized  to  the  carboxyl  group  the  first  step  was  to  prepare 
o- me  thy 1-m- isopropyl  benzoic  acid  from  acetocymene.  A strong 

1.  J.Ind.  and  3ng.  Chem.  11,  1130-1133 

2.  Chem.  News  47,  115 


I 


■ 


-6- 

strong  oxidiz&ng  agent  could  not  be  used  because  of  the  unstabil  ■ 
ity  of  the  isopropyl  group.  Directions  are  given  in  Noyes 
laboratory  Manual  for  the  oxidation  of  berjalacetone  to  cinn- 
amic acid  by  using  sodium  hypochlorite  as  the  oxidizing  agent. 

By  following  these  general  directions  with  the  exception  that  a 
more  concentrated  hypochlori te  solution  was  used  it  was  possible 
to  oxidize  acetocyrnene  to  o- me thy  1-m- isopropyl  benzoic  acid 
in  yields  exceeding  75  $•  This  acid  has  previously  been 
prepared’3'  by  heating  tricarvaCrol  phosphate  with  potassium 
cyanide  and  then  hydrolyzing  the  product.  This  reaction  is 

acc  omp  a n /ed 

^by  the  formation  of  many  impurities  which  make  it  much  more 
complicated  than  the  method  used  above. 

The  acid  thus  obtained  was  then  nitrated  under  the  same 
conditions  that  acetocyrnene  was  nitrated,  A pale  yellow 
compound  was  obtained  which  upon  recrystallization  from  50 $ 
alcohol  came  down  in  very  fine  needles,  clustering  to  form 
plates.  A mixed  melting  point  with  the  nitration  product  of 
actocymene  gave  a melting  point  which  was  the  same  as  that  of 
the  original  compound.  There  is  no  doubt  that  the  compound 
obtained  from  the  nitration  of  acetocyrnene  and  from  the  nitra- 
tion of  o-methyl-m-isopropyl  benzoic  acid  are  the  same.  There 
is,  however,  a marked  difference  in  the  yields  of  these  products, 
The  first  was  obtained  with  difficulty  with  a yield  of  15$, 
while  the  second  was  obtained  with  a yield  of  9 £$.  Here  we 
have  evidence,  surely,  of  a stabilizing  action. 

1.  B.  18,  1714 


J 


_ 


1 


* 


* 


-7- 


It  seems  highly  probable  that  the  carboxyl  group  meta 
to  the  isopropyl  group  stabilises  that  group  towards  the  action 
of  the  nitrating  agent. 

<P 

To  further  verify  the  assumption  that  the  - C -Q 
stabilizes  the  isopropyl  group  the  methyl  ester  of o-methyl- meta- 
isopropyl benzoic  acid  was  nitrated.  The  o-me thy 1-m- isopropyl 
benzoyl  chloride  was  first  prepared  and  this  on  treatment  with 

absolute  methyl  alcohol  gave  the  ester. 

a 

The  ester,  like  acetocymene,  is* high  boiling  liquid;  the 
characteristic  properties  of  these  two  compounds  are  closely 
related.  Yet,  aceto-cymene  on  nitration  forms  a gummy  mass 
from  v/hich  a definite  crystalline  compound  is  obtained  with 
difficulty,  while  the  ester  when  nitrated  under  exactly  the  same 
conditions,  reacts  very  smoothly  forming  a well  crystallized 
product.  The  difference  in  behavior  of  these  two  compounds  can 

fi 

be  explained  by  the  stabilizing  action  which  the  - C -0  group 
meta  to  the  isopropyl  group  has  towards  that  group. 

Alfthan^  in  his  article  states  that  2,3,6  trinitrocymene 

has  been  obtained  by  nitrating  cymene.  R.  Ritiig2  obtained  a 

0 

’trinitrocymene’  v/hich  melts  at  119  . Zaloziecki  also 
isolated  a ’trinitrocymene'  melting  at  126°,  while  Landolf^ 
obtained  a compound  which  he  also  calls  trinitrocymene  melting 
at  183.5°- 184. 5°.  It  is  the  belief  of  the  author  that  cymene 

3.  B.  27,  2065 

4.  B.  6,  938  (1873) 


1.  B.  53B,  180 

2.  A.  145,  142(1863) 


, 


. 


. 

' 


. 


-8- 


on  nitration  forms  dinljtrocymene  and  that  on  farther  nitration 
the  third  nitro  group  enters  the  side  chain  forming  a compound 
with  the  following  structure. 


The  2,6  dinitrocymene  was  prepared  and  then  nitrated.  The 
reaction  did  not  proceed  smoothly. 

Inc  connection  with  the  preparation  of  acetocymene  several 

runs  were  made  to  determine  whether  aluminum  chloride  in  the 
ffriedel  and  Craft’s  reaction  adds  on  as  A1C1,,  or  as  AlgCl  . If 


it  adds  on  as  AlgCl.  two  mols  would  have  to  he  used  to  obtain 
$he  product.  Two  runs  using  first  one  mol  and  then  two  mols  of 
aluminum  chloride  gave  yields  of  41/j  and  41.5;b  • Without  a 
question  only  one  mol  is  necessary  in  the  above  reaction. 

Butyl  derivatives  of  the  benzene  series,  especially  toluene 
and  xylene,  when  nitrated  form  very  good  artifice!  musks.  The 
introduction  of  a tertiaiy  bujyl  group  into  cymene  by  the  Friedel 
and  Craft’s  reaction  using  aluminum  chloride  was  tried  but  very 
poor  yields  were  obtained.  In  a recent  review  on  artifical 
musks'*' the  authors  state  that  to  intoduce  the  butyl  group  into 
the  benzene  ring  ferric  chloride  should  be  used  instead  of 

1.  Chemie  and  Ind.  6,  719 


ch3 


-9- 


aluminura  chloride.  The  failure  to  prepare  tertiary  butyl  cymene 
is  then  accounted  for. 

Acetoraesitylene  was  prepared  and  this  product  nitrated 
gave  a compound  with  a musk  odor. 


EXPERIMENTAL 


p-Cymol  methyl  ketone,  acetocymene 

To  480  gr.  of  cymene  ( 10  mols)  2000  c.c.  of  carbon, 
bisulphide  was  added.  The  mixture  was  kept  in  an  ice  bath.  To 
this  440  gr.  of  pulverised  aluminum  chloride  was  slowly  added. 
After  the  reaction  ceased  280  gr.  ( 10  mols)  of  acetyl  chloride 
was  added  drop  by  drop,  the  mixture  being  vigorously  stirred 
by  means  of  a mechanical  stirrer.  The  whole  was  allowed  to 
reflux  for  two  to  three  hours  until  all  the  hydrochloric  acid 
evolved  came  over.  The  carbon  bisulphide  was  then  quickly 
distilled  and  the  residue  poured  over  ice  water  to  remove  the 
aluminum  chloride.  The  dark  brown  oil  was  separated  and  ex- 
tracted with  ether.  The  ether  solution  was  washed  with  water 
and  then  dried  over  calcium  chloride.  The  dry  ether  solution 
was  then  distilled.  A clear,  yellow,  sweet  smelling  oil 
boiling  at  256°  - 260°,  uncorrected,  was  obtained.  Yield 
392  gr.,  62/o. 

Nitration  of  Ace to cymene 

To  20  gr.  of  acetocymene,  kept  at  0°  0.,  66  gr.  of  Tp 

fuming  sulphuric  acid  was  slowly  added.  The  ketone  slowly 

changed  its  color  until  quite  dark  brown  on  addition  of  all 

the  acid.  To  this  solution  34  gr.  of  fuming  nitric  acid  ( sp.  gr. 

1.50)  was  added  at  the  rate  of  30  drops  per  minute,  a mechanical 

stirrer  being  used.  After  all  of  the  acid  was  added  the  nitra- 
tion was  allowed  to  proceed  for  another  two  hours. 


, 


: 

■ 


' 


. 


, 

* 


. 


; , 


»■ 


’ 


-11- 


A dark  brown  mss  was  obtained  which  was  poured  over  ice  water 
and  thorougly  washed  from  all  acids.  The  final  product  which 
was  light  yellowr  in  color  formed  a gummy  mass.  After  standing- 
six  weeks  a crystalline  compound  was  isolated  from  carbon  tetra' 
chloride.  Yield  3 grams. 

Analysis  of  Nitration  Product 

Subs.  Q.1S86;  6.35  c.c.  of  0.1187  IT.  ITaOH  required. 

Subs.  0.E500,  0.4000;  C0g;266.8  c.c.,  428  c.c.;  Temp.  26°, 

23°  0.;  Pressure:  741.7  mm.,  734.2  mm. 

Subs.  0.2090;  N:  20.4  c.c.;  Temp.:  24°  C. ; 3ar.  741  mm. 

Calc,  for  Ci:LH1206IT2:  C,  49.2;  IT:  10.42;  N.E.  268 

Pound: G:  49.23;  2:  10.71;  N.B.  263 

n 49.51 

M.P.  182.5  , 183.5°,  183°. 

Oxidation  of  Nitrated  Coumpound 

1 gram  of  the  nitrated  product  was  dissolved  in  10  c.c.  of 
10/a  sodium  bicarbonate  solution.  To  this  5.5  gram  of  potassium 
permanganate,  dissolved  in  water  containing  3 c.c  of  10 fo  sodium 
hydroxide,  was  added.  The  mixture  was  allowed  to  refux  for 
twelve  hours.  At  the  end  of  this  period  the  manganese  dioxide 
was  filtered  off  and  any  impurities  soluble  in  ether  removed. 
The  residue  was  acidified  with  dilute  sulphuric  acid  and  the 
product  extracted  with  ether.  The  ether  was  distilled  off  and 
the  product  recrystallized  from  hot  water.  It  came  down  in 
fine  white  needles  melting  at  199°  - 200°  q. 


. 


-12- 


Analysis 

Subs:  0.23275;  22.14  c.c.  of  0.0909  N i£0H  required. 

Subs:  0.3014  gr. ; CO  , 310  c.c.:  Temp.  21. 8U  C. , Bar.  740.5im|. 
Subs:  0.1932;  N:  10.4  c.c.;  Temp.  25°  C. ; Bar.  746.8  mm. 

Calc,  for  CgK„0  N:  N.E. , 112.5;  C:  48;  N:  6.22 


found 


N.E. , 115.5;  C:  48.27;  N:  5.93 


o-LIethyl-m- Isopropyl  Benzoic  Acid 

To  450  gr.  of  chloride  of  lime  600  c.c.  of  water  was  added. 
To  this  550  gr.  of  sodium  carbonate  in  650  c.c.  of  water  was 
added.  The  mass  was  filtered  and  washed  once.  The  filtrate  was 
added  to  50  gr.  of  acetocymene  and  the  whole  refluxed  for  four 
hours,  keeping  the  temperature  at  80°  - 90°  C.  A mechanical 
stirrer  was  used.  At  the  end  of  the  reaction,  shown  by  the 
disappearance  of  the  oily  layer,  the  mixture  was  cooled  and  the 
uncombined  acetocymene  extracted  with  ether.  The  residue  was 
acidified  with  dilute  sulphuric  acid,  the  produce  extracted  with 
ether  and  then  recrystallized  from  50 °/o  alcohol.  It  came  down  in 
white  needles  clustering  into  plates.  M.P.  75°  C.  Yield  27.5  gr. 
55$.  15  gr.  of  acetocymene  was  recovered,  making  an  actual  yield 

of  78.5  $. 

Nitration  of  o-me thy 1-m- isopropyl  benzoic  acid 

To  5 gr.  of  the  acid,  kept  at  0°  G.  17  gr.  of  7$  fuming 
sulphuric  acid  was  slowly  added,  which  seems  to  dissolve  the 

product .forming  a brown  mixture.  To  this  mixture  8 gr.  of 
fuming  nitric  acid  (sp.  gr.  1.50)  was  added  drop  by  drop.  On 


• ■ ; , 


to 


- 13- 


add  i tion  of  the  nitric  acid  the  mixture  gradually  chanXged  to  a 
lemon  yellow  color*  It  was  allowed  to  mitrate  for  one  hour  after 
all  of  the  nitric  acid  was  added,  and  then  poured  over  ice  water 
and  thoroughly  washed*  Upon  recrystallization  from  50^  alcohol 
it  came  down  in  fine  white  crystals  melting  at  182°  G.  A Tftixbd 
melting  point  with  the  product  isolated  from  the  nitration  of 
acetocymene  gave  a melting  point  of  182°  * ITo  gummy  mass  was 
formed. 

o-Ifleizyl-m- isopropyl  benzoyl  chloride 

To  5 gr*  of  o-methyl-m- isopropyl  benzoic  acid  6 gr*  of 
finely  pulverized  phosphorous  pen tachlo ride  was  added*  The 
reaction  began  after  shaking  vigorously  and  heating  slightly  on 
the  steam  bath*  A dirty  yellow  liquid  was  formed  which ^as  distill- 
ed under  diminished  pressure  from  an  oil  bath.  The  excess  phos- 
phorous pen ta chloride  distilled  over  first  and  was  removed*  A 
light  greenish  yellow,  clear  liquid  having  a sharp  odor  and  boiling 

o , V 

at  153  (25  mm.)  was  obtained. 

Yield  2.5  gr. , 45.4 fo 

Analysis  of  Product 

To  15  c.c.  of  absolute  ethyl  elcohol  a definite  amount  of  the 
chloride  was  added.  To  this  solution  1 gr.  of  sodium  was  added, 
and  the  whole  refluxed  on  the  steam  bath  for  a half  hour.  A 
miliy  white  liquid  was  obtained.  The  alcohol  was  distilled  off 
and  the  residue  diluted  with  20  cc.  of  water  containing  2 c.c.  of 


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-14- 

conc.  HNOr. . The  solution  was  titrated  with  standard  silver  nitrate 
5 

using  ferrous  sulfate  as  the  indicator. 

Subs:  7559,  42.3  c.c.  of  0.0981  N AglTG-  required. 

Calc,  for  C__H__QC1:  Cl:  19.29y6.  Found  Cl:  19*51/6 

11  15 

Methyl  Ester  of  o-methyl-m- isopropyl  benzol c acid 

To  7 gr.  of  the  acid  chloride  10  c.c.  of  absolute  methyl 
alcohol  was  added,  and  the  whole  refluxed  for  eight  hours.  The 
liquid  obtained  was  distilled  under  diminished  pressure  using 
an  oil  bath.  A clear,  colorless  liquid  having  a very  pleasant 
odor  and  a boiling  point  of  132° (10  mm.)  was  obtained. 

Yield  5.9  gr.  86.876. 

Nitration  of  the  methyl  ester  of  O-methyl-m- isopropyl  benzoic  acid 
To  5.9  gr.  of  the  ester  19.7  gr.  of  7 '76  fuming  sulphuric 
acid  was  slowly  added,  keeping  the  solution  at  0°C  and  well 
stirred.  No  change  in  the  solution  was  noticed.  To  this  9.8  gr. 
of  fuming  nitric  acid  ( sp.gr.  1.50)  was  ad' ed  at  the  rate  cf  30 
droids  a minute.  The  solution  first  became  orange  yellow  then 
light  yellow  and  viscous  as  more  acid  wad  added.  After  the 
addition  of  the  nitric  acid  the  mixture  was  allowed  to  nitrate 
for  another  hour.  At  the  end  of  this  period  it  was  poured  over 
ice  and  thorougly  washed  until  free  from  acids.  It  was  recrystal- 
lized from  50/6  alcohol  coming  down  in  clustering  needles  which 
were  v/hite  when  freshly  formed,  but  which  turned  orange  on 


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standing.  M.P.  161°,  but  not  definite.  No  sticky  mass,  as  in 
the  nitration  of  acetocymene,  was  formed. 

2,6  Dinitrocymene 

To  25  gr.  of  p-cymene  100  gr.  of  sulfuric  acid  ( sp.  gr.  1.84) 
was  slowly  added.  The  solution  was  cooled  by  salt-ice  mixture 
and  well  stirred  by  a mechanical  stirrer.  On  addition  of  the 
acid  the  solution  became  yellow.  To  this  50  gr.  of  fuming  nitric 
acid  ( sp.  gr.  1.50)  was  added  drop  by  drop.  The  solution  became 
dark  brown.  It  was  allowed  to  nitrate  for  two  hours.  At  the 
end  of  this  period  it  was  poured  over  ice  water.  It  came 
down  as  a sticky  brownish  mass  which  was  extracted  with  ether 
and  thorougly  wrashed  with  v/ater  until  free  from  acids.  To  the 
ether  solution  50  c.c  of  10$  sodium  bicarbonate  solution  was  added 
Any  acids  that  may  have  formed  were  thus  removed.  The  ether 
soluble  portion  was  again  washed  and  then  dried  over  CaCig.  The 
ether  was  distilled  off  leaving  a clear,  rather  viscous,  reddish 
liquid.  Yield  25  gr. , 59.7$. 

Analysis 

Subs.  0.4148;  493.6  c.c.  CGg;  Temp.  30.2°;  Bar.  741.3 
Calc,  for  ci0H12°4K2:  G:  53*57'^  Found:  C:  53.51$ 

Nitration  of  2,6  Binitrocymene 

To  10  gr.  of  dinitrocymene  33  gr.  of  7 $ fuming  sulfuric 

acid  was  added.  The  solution  first  became  light  yellow  but  turned 
to  dark  boown  on  addition  of  all  of  the  acid.  To  this  17  gr.  of 

fuming  nitric  acid  (sp.  gr.  1.50)  was  added  drop  by  drop.  The 


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color  gradually  changed  to  yellow*  After  nitrating  for  an  hour 
the  product  was  poured  over  ice  water.  It  came  down  as  a gummy 
mass.  A solid  was  isolated  from  carbon  tetrachloride  which 
melted  at  approximately  £10°.  The  yield  was  poor. 

Ace tomes itylene 

50  grams  of  mesitylene  was  dissolved  in  200  c.c.  of  carbon 
bisulphide,  to  which  wa&  added  125  gr.  of  freshly  distilled 
acetyl  chloride.  By  using  a three  necked  flask  50  gr.  of 
finely  pulverized  aluminum  chloride  was  added  just  fast  enough  to 
keep  the  reaction  going.  The  mixture  was  mechanically  stirred 
and  allowed  to  react  for  one  hour.  The  carbon  bisulphide  was 
then  quickly  distilled  and  the  residue  poured  over  ice  water. 

The  oil  was  extracted  with  ether,  washed,  then  dried  over  calcium 
chloride  and  distilled.  A light  yellow,  clear  liquid  boiling  at 
235°  -237°  (uncorrected)  was  obtained.  Yield  48  grams.,  72;a  . 

The  reaction  should  not  be  allowed  to  proceed  for  more  than  one 
hour,  and  the  aluminum  chloride  must  be  added  slowly  to  obtain  a 
product  with  yields  over  70 'jo. 

Hitration  of  Ace tomes itylene 

To  10  gr.  of  aeetomesitylene  34  gr.  of  7$  fuming  sulfuric 
acid  was  added.  To  this  solution  17  gr.  of  fuming  nitric  acid 
(sp.  gr.  1.50)  was  added  drop  by  drop.  After  nitrating  for  an 

hour  the  product  was  poured  over  ice  water  and  thorough tly  washed. 
It  was  extracted  w ith  ether  and  the  ether  then  evaporated.  A 

light  brown  solid  melting  at  193°  with  darkening  v/as  obtained. 


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suiUAKV 

I*  Acetocymene  was  prepared  and  then  nitrated  using  fuming 
sulfuric  acid  and  fuming  nitric  acid(  sp.  gr.  1.50)  as  th^i  trating 
agent.  A crystalline  compound  was  isolated  with  difficulty. 

II.  The  structure  of  this  compound  was  determined.  The  -COOK^ 
group, was  oxidized  to  the  carboxyl  group,  one  nitro  group 
entered  the  side  chain  in  the  isopropyl  group  and  one  nitro 
group  entered  the  ring. 

III.  o-Me thy  1-in- isopropyl  benzoic  acid  was  prepared  and  then 
nitrated  under  the  same  condition  as  acetocymene.  The  nitration 
products  of  both  were  the  same,  the  yield  in  the  latter,  however, 
was  much  greater. 

IV.  The  methyl  ester  of  0-methyl-m- isopropyl  benzoic  acid  was 
nitrated  as  above  and  a solid  compound  obtained  without  the 
formation  of  side  products. 

v.  Some  evidence  was  collected  which  indicated  that  the  - 0 - 0 
group,  meta  to  the  isopropyl  group,  stabilizes  that  group  towards 
the  action  of  the  nitrating  agent  sulfuric  acid--nitric  acid. 

VI.  Ace tomes itylene  was  prepared  and  then  nitrated.  A compound 
smelling  of  mush  was  obtained. 


